1. Field of the Invention
The invention relates generally to Dickkopf (Dkk) proteins, functional fragments thereof, and more specifically to their functional activities related to cell migration, maturation and wound healing.
2. Background Information
Cancer remains one of the most significant health problems world wide, and ranks second only to heart disease as a leading cause of death in the United States. Cancer, for the most part, involves uncontrolled proliferation and altered differentiation of the involved cells. Although the causes of most cancers are not identified and the mechanisms remain obscure, human, epidemiological, and experimental efforts have generated considerable information on the attributes of cancer. Many factors that are normally important in cell growth and differentiation, as well as normal molecular signaling, in healthy individuals can contribute to the genesis or progression of the carcinogenic process in certain disease states.
Members of the Wnt family of signaling molecules have been implicated in the genesis and progression of several human cancers. Wnt signaling mediates cell growth and differentiation, as well as many patterning processes, during invertebrate and vertebrate development. The Wnt signaling pathway also plays an important role in the inductive interactions that regulate growth and differentiation, and also likely critical in the homeostatic maintenance of post-embryonic tissue integrity. Wnt stabilizes cytoplasmic β-catenin, which stimulates the expression of genes involved in cell growth and differentiation. As such, altered regulation of Wnt signaling can not only cause defects during development, but also affects the regulated growth and differentiation of cells following development.
Although progress is being made in understanding the biochemical and genetic mechanisms responsible for many cancers, very few successful treatment options currently exist. Unfortunately, even the most effective therapies have significant negative systemic side effects and toxicity that can be intolerable to the patient. Typical negative side effects can include, for example, nausea and vomiting, hair loss, anemia, depression of the immune system leading to infection and sepsis, and other toxic effects. Because these effects on a patient can sometimes be as debilitating as the disease being treated, the effectiveness of these current therapies is severely limited.
There is, therefore, a need for new methods and compositions for treating cancer. In particular, there is a need for treatment compositions and methods capable of inhibiting unregulated growth, differentiation and migration of cancer cells.